The laboratory has been studying the occurrence of mutations in the mitochondrial genome in the brain. The brain which relies heavily on aerobic metabolism requires functional mitochondria. These mitochondria are subcellular organelles with their own genome which codes for 13 essential protein subunits. Prior studies, employing limited numbers of clinical samples, reported an increase of mitochondrial DNA deletion mutations, mtDNA4977 with aging in regions of the brain. However, our Laboratory examined brain tissue from 43 age-comparable individuals (between ages 34 and 73), utilizing PCR assays and we found that these mutations correlated with conditions associated with chronic hypoxia rather than with aging. Higher levels of the mtDNA4977 in the putamen(12 fold), and the superior frontal gyrus of the cortex (5 fold), were found in individuals who had conditions associated with chronic hypoxia when compared with individuals without evidence of such conditions. These findings suggest that chronic hypoxia should be more closely examined in the pathophysiology of central nervous system diseases.